The project outlined in this application will focus on the molecular mechanism underlying mammalian odor perception through the investigations of specific anosmia and sensitization of androstenone and other ligands. Androstenone odorant receptor(s) will be identified using a screening system matching receptors to their cognate ligands. Such system will be strengthened by a structure-function analysis of the receptor- transporting proteins (RTPs). Deletion and chimeric series of RTPs will be assessed in cell-surface immunostaining and luciferase assay to identify key regions. Domains of interaction between RTPs and odorant receptors will be investigated using the split-ubiquitin yeast two-hybrid system. The polymorphisms in candidate androstenone odorant receptor(s) will be evaluated for correlation with the anosmic phenotype by genotyping a psychophysically-analyzed population. Mouse models of androstenone-anosmic and osmic strains will be used for similar SNP genotype analysis, as well as mRNA and protein expression analyses. In vivo sensitization and experiments in heterologous cell will shed lights how ligand exposure facilitates androstenone sensitization. [unreadable] [unreadable] [unreadable]